L5 L6 Dose Response Curves

Pharmacodynamics is the study of __ on the __. It includes the study of -

drug on the body. Includes drug targets, drug-receptor interactions, mechanisms of action, and corresponding side effects.

Quantal Dose-Response curves

minimum dose requires to cause a specific response measured in each individual ("all or none" binary response, not a graded response)

Graded Dose-Response curves

as the concentration of the drug increases, the magnitude of its biological effect also increases.

Affinity

The ability of a drug to bind to a receptor and the strength of the bond.

Dissociation constant (Kd)

Propensity of a drug to separate from the receptor (nmol/L).

Is affinity directly or inversely proportional to Kd?

inversely proportional to Kd.

Efficacy

The ability of the drug to elicit a response upon binding to the receptor.

Maximal effect (Emax)

Determines efficacy. The maximum effect achieved upon drug-receptor binding, assuming that all available receptors are drug bound, and addition of more drug will not increase the response.

(read Emax from y-axis)

Is efficacy directly or inversely proportional to Emax?

directly proportional to Emax.

Potency

The amount of drug necessary to produce and effect of a given magnitude.

(on a graph: left is more potent, right is less potent)

ED50

Determines potency. The concentration of drug producing 50% of the maximum drug response.

Is potency directly or inversely proportional to ED50?

inversely proportional to ED50.

Practice questions:

a) Drug A and B have equal ___ but different ____.

b) which drug has the highest potency

c) which drug has the lowest efficacy?

d) which drug has the highest affinity?

a) equal efficacy but different affinity.

b) drug A

c) drug C

d) cannot be determined

Therapeutic window

A range of doses that produce a therapeutic response without causing any significant adverse effect in patients.

Therapeutic index

A quantitative measurement of the relative safety of drugs.

TD50 / ED50

TD50 (Toxic dose 50)

the drug dose that produces a toxic response in half the population.

ED50 (Effective dose 50)

The drug dose that produces a desired therapeutic effect is half of the population.

T/F? A larger therapeutic index value implies that the drug is safer.

True

Agonist

Bind to a receptor to cause a pharmacological effect (have both affinity and intrinsic efficacy)

Antagonist

Bind to a receptor and inactivate it, resulting in decreased response of co-administered agonists. No change in constitutive activity, but blockade of agonist activity (only affinity and no intrinsic efficacy)

Full agonists

(at sufficient concentrations) activate receptors to the maximum extent (high intrinsic efficacy)

Partial agonists

(even at high concentrations) also activate receptors the same way, but do not generate as high of a response (low intrinsic efficacy)

Inverse agonists

Bind to a receptor to cause a pharmacological effect opposite to that seen with an agonist.

Competitive antagonists

Effects? Shifts? Can the effects be overcome?

reversible effects

shift the DRC to the right (affects potency)

Can be overcome, by increasing the concentration of the agonist.

Non-competitive antagonists

Effects? Shift? Can the effects be overcome?

Irreversible

Shift the DRC downwards. (affects efficacy)

Cannot be overcome.